GEO series

Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8 T cells [dataset 1]

GSE272993 Homo sapiens Expression profiling by high throughput sequencing; Other 360 samples Submitted 2024/07/30 Platform GPL24676

Summary

Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism in humans remains unclear. We performed RNA+TCR single-cell analysis across time in 36 stage IV melanoma patients treated with anti-PD-1, anti-CTLA-4, or combination therapy. We developed the algorithm Cyclone to track temporal clonal dynamics and underlying cell states. Checkpoint blockade induced waves of clonal T cell responses that peaked at distinct timepoints. Combination therapy resulted in greater magnitude of clonal responses at 6 and 9 weeks compared to single-agent therapies, including melanoma-specific CD8 T cells and exhausted CD8 T cell (TEX) clones. Focused analyses of TEX identified that anti-CTLA-4 induced robust expansion and proliferation of progenitor TEX, which synergized with anti-PD-1 to reinvigorate TEX during combination therapy. These next generation immune profiling approaches can guide the selection of drugs, schedule, and dosing for novel combination strategies.

Published in

Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8(+) T cells

Wang K, Coutifaris P, Brocks D et al. · Cancer cell 2024 · PMID 39214097 · doi:10.1016/j.ccell.2024.08.007

This dataset

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Direct links to NCBI, no account and no request form: the whole study as GSE272993_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 360 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1138883 and SRA study SRP521777. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39214097) ↗

Study design

9 conditions, mostly with about 5 replicates each

Feature-2020-08-17-1 ×6 TCR-2020-08-17-1 ×6 Feature-2020-07-10-1 ×5 GEX-2020-07-10-1 ×5 TCR-2020-07-10-1 ×5 GEX-2020-08-17-1 ×4 Feature-2020-08-19-1 ×3 GEX-2020-08-19-1 ×3 +1 more

Supports a between-group comparison across 40 samples.

9 replicated groups read from the first 40 of 360 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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